| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Internal Medicine, University of Iowa, Iowa City, Iowa, USA
2 Internal Medicine, University of Iowa, Iowa City, Iowa, USA; Electrical Engineering, University of Iowa, Iowa City, Iowa, USA
3 Mechanical, Aerospace, and Biomedical Engineering, University of Tennessee, Knoxville, Tennessee, USA
4 Electrical Engineering, University of Iowa, Iowa City, Iowa, USA
5 Internal Medicine, University of Iowa, Iowa City, Iowa, USA; Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
* To whom correspondence should be addressed. E-mail: alan-moy{at}uiowa.edu.
The cytoskeleton is critical to the viral life cycle. Agents like cytochalasin inhibit viral infections, but cannot be used for antiviral therapy because of their toxicity. We report the efficacy, safety and mechanisms by which gene delivery of human wild-type low molecular weight caldesmon (l-CaD) protects cell-membrane integrity from adenovirus infection in a DF-1 cell line, an immortalized avian fibroblast that is null for l-CaD. Transfection with an adenovirus (Ad) controlled- construct mediated a dose-dependent decline in transcellular resistance. Using a computational model of cytoskeletal-membrane properties, Ad disturbed cell-cell and cell-matrix adhesion and membrane capacitance. Transfection with the Ad-l-CaD construct attenuated Ad-mediated loss in transcellular resistance. Quantitation of vinculin-stained plaques revealed an increase in total focal contact mass in monolayers transfected with the Ad-l-CaD construct. Expression of l-CaD protected transcellular resistance through primary effects on membrane capacitance, and independent of actin solubility and of effects on prestress as measured by the decline in isometric tension in response to cytochalasin D. Expression of l-CaD exhibited less trypan-blue cell toxicity than cytochalasin, and, unlike cytochalasin, it did not interfere with wound closure or adversely effect transcellular resistance. This demonstrates the potential of gene delivery of wild-type human l-CaD as a potentially efficacious and safe agent that inhibits some of the cytopathic effects of adenovirus.
This article has been cited by other articles:
|
|
 |
|
  A. B. Moy, K. Blackwell, M. H. Wu, and H. J. Granger Growth factor- and heparin-dependent regulation of constitutive and agonist-mediated human endothelial barrier function Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2126 - H2135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gardet, M. Breton, P. Fontanges, G. Trugnan, and S. Chwetzoff Rotavirus Spike Protein VP4 Binds to and Remodels Actin Bundles of the Epithelial Brush Border into Actin Bodies. J. Virol., April 1, 2006; 80(8): 3947 - 3956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Bodmer, A. English, M. Brady, K. Blackwell, K. Haxhinasto, S. Fotedar, K. Borgman, E.-W. Bai, and A. B. Moy Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series Am J Physiol Cell Physiol, September 1, 2005; 289(3): C735 - C747. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
